In this grant cycle, The Children's Hospital of Philadelphia (CHOP) will continue its previous 30 years of contributions to CCG. Specifically, CHOP will enter large numbers of patients on therapeutic trials, diligently supply patient samples for biologic and translational studies, carry out both institutional and CCG-linked pilot studies, and provide a vast and varied repetoire of young and mature talent and scientific leadership. In the past cycle, CHOP's Neuro-Oncology pilot studies were templates for 4 CCG Phase I and Phase II studies. In this cycle the Neuro-Oncology Program will introduce novel routes of delivery, targetted therapy, and exploration of neurofibromatosis type 1(NF-1) to probe the interface of genetics and brain tumors. In collaboration with the Neuro-Oncology Program, the Neuroblastoma Program will develop the TRK group of receptors for diagnosis prognosis and therapy. Based on CHOP pilot studies, the Leukemia Group will propose to CCG protracted, reduced-dose craniospinal irradiation of CNS relapse and established CNS disease and will introduce the repetitive reinduction/reconsolidation strategy for marrow relapse. CCG- supported CHOP laboratory investigation in leukemia includes genetic epidemiology of treatment-related leukemias and infant leukemia and the pediatric myelodysplastic and myeloproliferative syndromes. The CHOP Solid Tumor Group's pilot study of interval compression is being incorporated into the next phase III Ewing's trial. PCR analysis of t(2;13) and other fusion genes will be used for detection of minimal residual disease and for development of targetted therapy. The Division of Oncology's new Experimental Therapeutics Program will investigate unique biologics such as the HLA independent TALL-104 cell line, TRK targetted CEP-751, and IGFR soluble receptor and antisense the IGF1 receptor. CHOPs Transition Program aims to be a prototype for follow-up of survivors, promoting good preventive health strategies and good research. The first transition study seeks to define predisposing genetic risk factors in patients who have second malignant neoplasms. The interactions of CHOP and CCG are bidirectional and are mutually rewarding for both.